Motor neuron disease clinically limited to the lower motor neuron is a diffuse TDP-43 proteinopathy
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Felix Geser Beth Stein Michael Partain Lauren B. Elman Leo F. McCluskey Sharon X. Xie Vivianna M. Van Deerlin Linda K. Kwong Virginia M.
- چاپ و سال / کشور: 2011
Description
Motor neuron disease (MND) may present as an isolated lower motor neuron (LMN) disorder. Although the significance of pathological 43 kDa transactive responsive sequence DNA binding protein (TDP-43) for amyotrophic lateral sclerosis (ALS) was appreciated only recently, the topographical distribution of TDP-43 pathology in MND clinically isolated to the LMN versus normal controls (COs) is only incompletely described. Therefore, we performed longitudinal clinical evaluation and retrospective chart review of autopsied patients diagnosed with isolated LMN disease. Cases with a disease duration over 4 years were designated as progressive muscular atrophy (PMA), and those with a more rapid course as MND/LMN. Immunohistochemistry was employed to identify neuronal and glial TDP-43 pathology in the central nervous system (CNS) in patients and COs. We examined 19 subjects including six patients (i.e., four with MND/LMN and two with PMA) and 13 COs. All patients showed significant TDP-43 linked degeneration ofLMNs, and five cases showed a lesser degree of motor cortex degeneration. Additional brain areas were affected in varying degrees, ranging from predominantly brainstem pathology to significant involvement of the whole CNS including neocortical and limbic areas. Pathological TDP-43 was present only rarely in the CO group. We conclude that MND limited to the LMN and PMA is part of a disease continuum that includes ALS and FTLD-TDP, all of which are characterized by widespread TDP-43 pathology. Hence, we suggest that the next revision of the El Escorial criteria for the diagnosis of ALS include MND patients with disease clinically limited to theLMNandPMAas variants of ALS, which like classical ALS, are TDP-43 proteinopathies
Acta Neuropathol (2011) 121:509–517 DOI 10.1007/s00401-011-0797-z Received: 1 December 2010 / Revised: 20 December 2010 / Accepted: 21 December 2010 / Published online: 12 January 2011
